The electrophysiologic actions of cellular constituents, their metabolites, and analogues of membrane constituents on the cardiac cell are only poorly understood. Recent studies indicated such factors to be of importance in cardiac disease. Certain metabolites, such as lysophosphoglycerides, accumulate in the ischemic myocardium and have electrophysiologic actions related to cardiac arrhythmias. Other constituents, such as acyl carnitine, seem to have similar actions in the ischemic myocardium. Oxygenated sterol compounds (OSC) affect sterol synthesis and can insert into the cellular membrane. OSC may have a physiologic role and they are being tested in experimental animals to control the lipoprotein profile and to lower cholesterol esters. Our preliminary studies suggest that one of the lysophosphoglycerides lysophosphatidylcholine (LPC), and OCS to have similar effects on cardiac excitability in the sheep cardiac Purkinje fiber using the multiple microelectrode techniques of intracellular constants current application and voltage clamping. These techniques permit selective control of numerous electrophysiologic variables and allow direct assessment of the determinants of cardiac excitibility such as membrane ionic conductances, active membrane generator properties, cable properties, and other membrane characteristics. Although these quantitative electrophysiologic techniques have been available for some time and have been instrumental in advancing our knowledge of basic electrophysiology, they have been little used in the study of arrhythmogenesis except by the applicant and a few others. Computer modeling of membrane events will be used to assess the magnitude of error in the measurements and otherwise assist in the interpretation of data. This investigation will be both of basic and clinical significance. In the long run, these studies should suggest therapeutically useful interventions in the treatment of the life-threatening cardiac arrhythmias associated with ischemic heart disease.